Conditional fusogenic lipid nanocarriers for cytosolic delivery of macromolecular therapeutics DOI Open Access
Qian Zhong, Edward K.W. Tan,

Ananth Shyamal

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Abstract Macromolecular therapeutics designed for intracellular targets must overcome systemic delivery barriers, target cell membrane impermeability, and inefficient endosomal escape. Here, we engineer a class of conditional fusogenic liposomes (C-FLIPs) that harness the catalytic activity extracellular proteases present in pathological microenvironment. This context-specific activation enables on-target fusion with cells diseased tissue, resulting cytosolic therapeutic payloads. We describe cytoplasmic three prototypic macromolecular classes: peptide degraders, cytotoxic proteins, ribonucleoprotein particles (RNPs). further develop C-FLIP to deliver granzyme B (GzmB) cytoplasm cancer vivo induce pyroptosis immunologically-inert tumors. Treatment C-FLIP/GzmB reprograms immunosuppressive tumor microenvironment synergizes checkpoint blockade result regression established tumors immunological memory. modular, non-viral, platform represents promising approach leverage protease targeted biologics.

Language: Английский

Design of pH-Responsive Nanomaterials Based on the Tumor Microenvironment DOI Creative Commons

Yunheng Liu,

Lei Si, Yuxuan Jiang

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 705 - 721

Published: Jan. 1, 2025

The metabolic activity of tumor cells leads to the acidification surrounding microenvironment, which provides new strategies for application nanotechnology in cancer therapy.Researchers have developed various types pH-responsive nanomaterials based on acidic microenvironment.This review an in-depth discussion design mechanisms, drug-loading strategies, and pathways microenvironment-responsive nanodrug delivery systems.These materials trigger drug release upon reaching enhancing therapeutic targeting reducing toxicity healthy cells.pH-responsive include organic nanomaterials, inorganic composite nanomaterials.Additionally, this outlines prospects, challenges aiming promote development clinical translation field.

Language: Английский

Citations

3
Nanocarriers for cancer-targeted delivery based on Pickering emulsions stabilized by casein nanoparticles DOI

Avital Ella Ben‐Haim,

Nurit Shalev,

Antolin Jesila Jesu Amalraj

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140822 - 140822

Published: Feb. 1, 2025

Language: Английский

Citations

2
The Impact of Metabolic Rewiring in Glioblastoma: The Immune Landscape and Therapeutic Strategies DOI Open Access

Yuganthini Vijayanathan,

Ivy A. W. Ho

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 669 - 669

Published: Jan. 14, 2025

Glioblastoma (GBM) is an aggressive brain tumor characterized by extensive metabolic reprogramming that drives growth and therapeutic resistance. Key pathways, including glycolysis, lactate production, lipid metabolism, are upregulated to sustain survival in the hypoxic nutrient-deprived microenvironment (TME), while glutamine tryptophan metabolism further contribute phenotype of GBM. These alterations impair immune cell function, leading exhaustion stress CD8+ CD4+ T cells favoring immunosuppressive populations such as regulatory (Tregs) M2-like macrophages. Recent studies emphasize role slow-cycling GBM (SCCs), lipid-laden macrophages, tumor-associated astrocytes (TAAs) reshaping GBM’s landscape reinforcing evasion. Genetic mutations, Isocitrate Dehydrogenase (IDH) Epidermal Growth Factor Receptor (EGFR) amplification, Phosphotase Tensin Homolog (PTEN) loss, drive offer potential targets for therapy. Understanding relationship between suppression critical overcoming This review focuses on rewiring GBM, its impact microenvironment, combining targeting with immunotherapy improve clinical outcomes patients.

Language: Английский

Citations

1
Targeting Metabolic Vulnerabilities to Combat Drug Resistance in Cancer Therapy DOI Open Access

Taranatee Khan,

M Nagarajan,

Irene Kang

et al.

Journal of Personalized Medicine, Journal Year: 2025, Volume and Issue: 15(2), P. 50 - 50

Published: Jan. 27, 2025

Drug resistance remains a significant barrier to effective cancer therapy. Cancer cells evade treatment by reprogramming their metabolism, switching from glycolysis oxidative phosphorylation (OXPHOS), and relying on alternative carbon sources such as glutamine. These adaptations not only enable tumor survival but also contribute immune evasion through mechanisms reactive oxygen species (ROS) generation the upregulation of checkpoint molecules like PD-L1. This review explores potential targeting metabolic weaknesses in drug-resistant cancers enhance therapeutic efficacy. Key pathways involved resistance, including glycolysis, glutamine kynurenine pathway, are discussed. The combination inhibitors with (ICIs), particularly anti-PD-1/PD-L1 therapies, represents promising approach overcoming both mechanisms. Clinical trials combining therapies have shown early promise, further research is needed optimize combinations identify biomarkers for patient selection. In conclusion, metabolism blockade offers novel drug providing pathway improved outcomes Future directions include personalized treatments based profiles expanding other types.

Language: Английский

Citations

1
The emerging role of glycolysis and immune evasion in ovarian cancer DOI Creative Commons
B. Jin, Zheng Miao, Junjie Pan

et al.

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 5, 2025

Ovarian cancer (OC) is one of the three most common malignant tumors female reproductive system, with highest mortality rate among gynecologic malignancies. Like other tumors, OC cells undergo metabolic reprogramming phenomenon and convert glucose metabolism into "aerobic glycolysis" generate a high concentration lactate, i.e., "Warburg effect", which provides large amount energy corresponding intermediary metabolites for their survival, reproduction metastasis. Numerous studies have shown that targeted inhibition aerobic glycolysis lactate promising strategy to enhance sensitivity immunotherapy. Therefore, this review summarizes features in highlights how abnormal affects differentiation, metabolism, function infiltrating immune cells, contributes immunosuppression, may be potential therapeutic efficacy OC.

Language: Английский

Citations

1
Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma DOI Creative Commons
Jiao Wang, Chengyu Liu, Rong‐Hua Hu

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 1, 2024

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and accounts for more than 90% primary liver cancer. The advent immune checkpoint inhibitor (ICI)-related therapies combined with angiogenesis inhibition has revolutionized treatment HCC in late-stage unresectable HCC, as ICIs alone were disappointing treating HCC. In addition to altered microenvironment, abnormal lipid metabolism been extensively characterized various types Stains are known their cholesterol-lowering properties long history hypercholesterolemia reducing cardiovascular disease risk. Apart from ICI other conventional therapies, statins frequently used by advanced patients dyslipidemia, which often marked accumulation cholesterol fatty acids liver. Supported a body preclinical clinical studies, may unexpectedly enhance efficacy therapy through regulation inflammatory responses microenvironment. This review discusses changes summarizes evidence benefits stain use prospects possible mechanistic actions transforming microenvironment when immunotherapies. Consequently, statin emerge novel valuable adjuvant immunotherapies

Language: Английский

Citations

5
Oncomatrix: Molecular Composition and Biomechanical Properties of the Extracellular Matrix in Human Tumors DOI Creative Commons
Ilya Klabukov, Anna N. Smirnova, A. O. Yakimova

et al.

Journal of Molecular Pathology, Journal Year: 2024, Volume and Issue: 5(4), P. 437 - 453

Published: Oct. 5, 2024

The extracellular matrix is an organized three-dimensional network of protein-based molecules and other macromolecules that provide structural biochemical support to tissues. Depending on its properties, the influences cell adhesion signal transduction and, in general, can influence differentiation proliferation through specific mechanisms chemical mechanical sensing. development body tissues during ontogenesis accompanied by changes not only cells but also composition properties matrix. Similarly, tumor carcinogenesis a continuous change cells, called ‘oncomatrix’, as matures, from primary focus stage metastasis. In this paper, characteristics are considered, well evolution patterns be used biomarkers oncological diseases potential targets for promising anti-tumor therapies.

Language: Английский

Citations

5
pH-tailored delivery of a multitarget anticancer benzimidazole derivative using a PEGylated β-cyclodextrin-curcumin functionalized nanocomplex DOI
Heba Shawky, Dalia B. Fayed, Noha E. Ibrahim

et al.

Biomaterials Advances, Journal Year: 2024, Volume and Issue: 163, P. 213964 - 213964

Published: July 22, 2024

Language: Английский

Citations

4
From metabolic byproduct to immune modulator: the role of lactate in tumor immune escape DOI Creative Commons

Meng‐Lin Jiang,

Yuanchun Wang, Xiaoyong Zhao

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 25, 2024

Lactic acid, a key metabolic byproduct within the tumor microenvironment, has garnered significant attention for its role in immune evasion mechanisms. Tumor cells produce and release large amounts of lactic acid into microenvironment through aberrant glycolysis via Warburg effect, leading to drop pH. Elevated levels profoundly suppress proliferation capacity, cytotoxic functions, migratory abilities effector such as macrophages natural killer at site. Moreover, can modulate expression surface molecules on cells, interfering with their recognition attack it regulates signaling pathways that promote expansion enhanced function immunosuppressive like regulatory T thereby fostering tolerance microenvironment. Current research is actively exploring strategies targeting metabolism ameliorate evasion. Key approaches under investigation include inhibiting activity critical enzymes production reduce synthesis or blocking lactate transporters alter intracellular extracellular distribution. These methods hold promise when combined existing immunotherapies checkpoint inhibitors chimeric antigen receptor T-cell therapies enhance system's ability eliminate cells. This could pave way novel combinatorial treatment clinical cancer therapy, effectively overcoming phenomena, ultimately improving overall efficacy.

Language: Английский

Citations

4
pH of Microenvironment Directly Modulates the Phenotype and Function of Cancer-Associated Fibroblasts DOI Creative Commons
Ying Li, Chao He, Aiguo Shen

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Cancer-associated fibroblasts within the tumor microenvironment have been studied extensively, including their differential roles in promoting cancer growth and metastasis, an immune suppressive microenvironment, reshaping stiffness of extracellular matrix. Fibroblasts diverse functions owing to heterogeneous phenotypes shaped by microenvironment. Increased acidity is a crucial feature contributing generation cancer-associated fibroblasts. Our data show that low pH drives formation vitro, while increasing activates self-remodeling features these cells limiting proliferation downregulating production matrix-associated proteins. findings are versatile population can be reprogramed toward quiescent phenotype with reduced regulation could potential strategy target for therapy.

Language: Английский

Citations

0